selinexor plus combination chemotherapy in treating patients with advanced b cell non-hodgkin lymphoma

Conditions: Diffuse Large B-Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Extranodal Marginal Zone Lymphoma; Recurrent Follicular Lymphoma; Recurrent Indolent Adult Non-Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Waldenstrom Macroglobulinemia; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Extranodal Marginal Zone Lymphoma; Refractory Follicular Lymphoma; Refractory Mantle Cell Lymphoma; Stage III Non-Hodgkin Lymphoma; Stage IV Non-Hodgkin Lymphoma; Transformed Recurrent Non-Hodgkin Lymphoma

Summary: this phase ib/ii trial is aimed at studying the combination of a drug named selinexor (selective inhibitor of nuclear export) in combination with standard therapy for b cell non-hodgkin's lymphoma called r-chop. the investigators will establish maximum tolerated dose of selinexor in combination with rchop and also study the efficacy of this combination for therapy of b cell non-hodgkin's lymphoma. giving selinexor plus chemotherapy may work better in treating patients with b cell non-hodgkin lymphoma.

the study will be done in two phases namely phase 1b and phase 2. in the phase 1b component the investigators intend to enroll patients in a 3+3 dose escalation design. newly diagnosed indolent and diffuse large cell lymphomas as well as relapsed/refractory indolent b cell lymphomas are eligible for enrollment in the phase 1 component. the primary end-point for this component would be to establish the recommended phase 2 dose (rp2d) for selinexor in combination with standard dose rchop chemotherapy. in the phase 2 part of the study the investigators will use recommended phase 2 dose of selinexor plus standard dose rchop combination to treat newly diagnosed dlbcl patients with the primary end-point being 2 year progression free survival. maintenance phase: patients with follicular lymphoma and diffuse large b cell lymphoma able to achieve pr or better at the end of therapy scan will be put on maintenance selinexor for a total of one year. the dose of selinexor in the maintenance phase would be similar to the last dose used for that particular patient in the treatment phase 1 or 2.

Eligibility criteria:
inclusion criteria: * phase 1 part: patients with pathologically confirmed advanced stage b-cell nhl (ann arbor stage 3 or 4) for whom r-chop is considered appropriate therapy; newly diagnosed dlbcl, newly diagnosed low grade b cell nhl, and previously treated low grade b cell nhl patients in first relapse after a prior treatment with non-anthracycline containing chemotherapy are allowed; double hit and transformed diffuse large b cell lymphoma are allowed \* allowed low grade b cell lymphomas will include follicular lymphoma any grade, marginal zone lymphoma including mucosa-associated lymphoid tissue (malt) lymphoma, indolent mantle cell lymphoma and waldenstrom's macroglobulinemia * phase 2 part: patients with pathologically confirmed newly diagnosed diffuse large b cell lymphoma (ann arbor stage 3 or 4); newly diagnosed double hit and transformed diffuse large b cell lymphoma are allowed * patients must have measurable disease, defined as at least one lesion above and below the diaphragm or stage 4 disease that can be accurately measured in at least one dimension; lymph nodes should be considered abnormal if the long axis is \> 1.5 cm, regardless of the short axis * allowed prior therapy: * newly diagnosed dlbcl and low grade b cell lymphoma: no prior therapy is allowed except steroids equivalent to maximum of prednisone 20 mg once daily for maximum of seven days prior to registration * relapsed/refractory low grade b cell lymphoma (only allowed in phase i): a minimum and maximum of one line of prior non-anthracycline containing therapy is allowed; prior localized radiation therapy is not considered a line * for patients who have had prior chemotherapy or immunotherapy, at least 2 weeks must have elapsed between last dose and initial dose of rchop-selinexor; for patients treated with radio-immunotherapy, at least 12 weeks * all races and ethnic groups are eligible for this trial * eastern cooperative oncology group (ecog) performance status =\ = 60%) * life expectancy of greater than 6 months * premenopausal female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential; acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal; for both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose * ability to understand and the willingness to sign a written informed consent document exclusion criteria: * patients with dlbcl who have received chemotherapy or immunotherapy (except one week of steroids as described above) at any time point in the past for therapy of the dlbcl; patients with low grade b cell lymphomas who have received more than one prior line of chemotherapy or any anthracycline-containing therapy in the past for their low grade b cell lymphoma; localized radiation therapy does not count as a line of therapy * patients who are receiving any other investigational agents * patients with known brain metastases are excluded * history of severe allergic reactions (as determined by treating physician) attributed to the drugs being used in the study * uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure (new york heart association \[nyha\] class \>= 3 or left ventricular ejection fraction \< 45%), unstable angina pectoris, myocardial infarction within the last 3 months, clinically significant cardiac arrhythmia (i.e., ventricular tachycardia on anti-arrhythmia are excluded; 1st degree atrioventricular \[av\] block or asymptomatic left anterior fascicular block \[lafb\]/right bundle branch block \[rbbb\] permissible), or psychiatric illness/social situations that would limit compliance with study requirements * pregnant and lactating women are excluded * human immunodeficiency virus (hiv)-positive patients regardless of treatment are excluded; patients with evidence of active hepatitis b and hepatitis c infection with positive real time polymerase chain reaction (qpcr) are also excluded but patients with prior exposure to hepatitis b or c with negative qpcr are allowed * patients with severe intolerance to glucocorticoids * major surgery within 2 weeks of first dose of study drug * patients who are unable to swallow tablets, patients with malabsorption syndrome, or any other gastrointestinal (gi) disease or gi dysfunction that could interfere with absorption of study treatment * absolute neutrophil count (anc) \< 1500 cells/mm\^3 * platelet count \< 100,000/mm\^3 * serum bilirubin \> 1.5 times the upper limit of normal (uln) (except patients with gilbert's syndrome: total bilirubin of \> 3 x uln) * alanine aminotransferase (alt) and aspartate aminotransferase (ast) \> 2.5 times uln * estimated creatinine clearance of \< 30 ml/min, calculated using the formula of cockroft and gault